Natural fluctuations in estrogens have been associated with a number of affective disorders in humans. In particular, low levels of circulating estrogens are associated with increased symptoms of depression, anxiety and cognitive dysfunction, which can often be ameliorated with hormone replacement therapy. Little is known about the mechanisms or the sites of action through which estrogen is influencing emotion, however, they likely occur within the amygdala. Therefore, a comprehensive analysis of the effects of estrogen within the amygdala is needed to further our understanding of how this steroid hormone influences the development of neuropsychiatric disorders in humans. The goal of the current proposal is to (I) determine the genomic and neurochemical actions of estrogen within the amygdala and (II) how they influence fear and anxiety in female rodents. This will be accomplished by examining estrogen-induced changes in gene expression within each region of the amygdala using quantitative-real-time-PCR (Q-PCR). These experiments will be followed by functional studies in which gene function knockdown with a novel antisense oligonucleotide moiety will be used to examine how estrogen-regulated genes influence fear and anxiety. These data will contribute to our knowledge of the hormonal mechanisms underlying fear and anxiety.